Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics
In this study, the phase I hepatic metabolism pathway of a cardiovascular drug nebivolol was proposed on the basis of a human liver microsomes assay with the use of LC-HR-MS coupled with the chemometric method. Six biotransformation products were found with the assistance of chemometric analysis. Fi...
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MDPI AG
2022-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/3/763 |
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| author | Jakub Trawiński Michał Wroński Maciej Gawlik Robert Skibiński |
| author_facet | Jakub Trawiński Michał Wroński Maciej Gawlik Robert Skibiński |
| author_sort | Jakub Trawiński |
| collection | DOAJ |
| description | In this study, the phase I hepatic metabolism pathway of a cardiovascular drug nebivolol was proposed on the basis of a human liver microsomes assay with the use of LC-HR-MS coupled with the chemometric method. Six biotransformation products were found with the assistance of chemometric analysis. Five of them were identified as the previously reported products of alicyclic hydroxylation and dihydroxylation, aromatic hydroxylation, as well as alicyclic oxidation of the parent compound. Moreover, one metabolite, not reported so far, was found to be a product of N-dealkylation of nebivolol—2-amino-1-(6-fluoro-3,4-dihydro-2<i>H</i>-1-benzopyran-2-yl)ethan-1-ol. The novel metabolite was submitted to an in silico toxicity analysis to assess its biological properties. The applied computational methods indicated a significantly elevated risk of its mutagenic activity, compared to the parent molecule. Several metabolites of the nebivolol described in the literature were not detected in this study, indicating their non-hepatic origin. |
| first_indexed | 2024-03-09T23:29:16Z |
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| id | doaj.art-7329050a9e834c0a9ff87f4e33884a56 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T23:29:16Z |
| publishDate | 2022-01-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-7329050a9e834c0a9ff87f4e33884a562023-11-23T17:12:04ZengMDPI AGMolecules1420-30492022-01-0127376310.3390/molecules27030763Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and ChemometricsJakub Trawiński0Michał Wroński1Maciej Gawlik2Robert Skibiński3Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, PolandDepartment of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, PolandDepartment of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, PolandDepartment of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, PolandIn this study, the phase I hepatic metabolism pathway of a cardiovascular drug nebivolol was proposed on the basis of a human liver microsomes assay with the use of LC-HR-MS coupled with the chemometric method. Six biotransformation products were found with the assistance of chemometric analysis. Five of them were identified as the previously reported products of alicyclic hydroxylation and dihydroxylation, aromatic hydroxylation, as well as alicyclic oxidation of the parent compound. Moreover, one metabolite, not reported so far, was found to be a product of N-dealkylation of nebivolol—2-amino-1-(6-fluoro-3,4-dihydro-2<i>H</i>-1-benzopyran-2-yl)ethan-1-ol. The novel metabolite was submitted to an in silico toxicity analysis to assess its biological properties. The applied computational methods indicated a significantly elevated risk of its mutagenic activity, compared to the parent molecule. Several metabolites of the nebivolol described in the literature were not detected in this study, indicating their non-hepatic origin.https://www.mdpi.com/1420-3049/27/3/763chromatographymass spectrometrydrug metabolismbiotransformationHLMtoxicity |
| spellingShingle | Jakub Trawiński Michał Wroński Maciej Gawlik Robert Skibiński Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics Molecules chromatography mass spectrometry drug metabolism biotransformation HLM toxicity |
| title | Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics |
| title_full | Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics |
| title_fullStr | Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics |
| title_full_unstemmed | Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics |
| title_short | Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics |
| title_sort | identification of the new metabolite of nebivolol using liquid chromatography coupled with high resolution mass spectrometry and chemometrics |
| topic | chromatography mass spectrometry drug metabolism biotransformation HLM toxicity |
| url | https://www.mdpi.com/1420-3049/27/3/763 |
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